Cryptococcus neoformans is a pathogenic yeast which belongs to Basidiomycetes, a taxonomic Class phylogenetically remote from the rest of the pathogenic yeasts (Ascomycetes). C. neoformans causes fatal meningoencephalitis primarily in patients with T- lymphocyte dysfunction and is the only species in the genus Cryptococcus that has optimum growth at temperatures higher than 30C. Although extensive studies on the molecular basis of cell cycle and morphogenesis have been carried out in ascomycetous yeasts, such studies have not been conducted in C. neoformans. This project was initiated to study the molecular genetics of cell cycle associated genes in C. neoformans. In 2003, we reported the function of the gene CCN1 which was necessary for the cell growth at 37C.This year, we cloned and deleted TUP1, a global regulator, which is known to control morphogenesis in many ascomycetous fungi from serotype D strains of C. neoformans and characterized the phenotype of tup1 deletants in both mating types. Unlike in other fungi, the TUP1 homolog played no role in cryptococcal morphogenesis. However, TUP1 was found to regulate sexual reproduction, resistance toward high concentration of cations and growth at temperatures below 30C. Most importantly, TUP1 was found to function differently in two mating types. Deletion of TUP1 from MATa strains caused a decrease in virulence while it had no effect in MATalpha strains and caused sensitivity toward high concentration of potassium chloride in MATalpha and it had no effect on cation sensitivity in MATa strains. These observations suggest that there is biological disparity betweem MATa and MATalpha strains of C. neoformans.